Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Somatostatin receptor agonist formulations

A receptor agonist and growth-stimulating hormone technology, applied in the direction of anti-inflammatory agents, liposome delivery, non-central analgesics, etc., can solve the problems of active agent concentration limitation and hysteresis

Active Publication Date: 2015-04-01
CAMURUS AB
View PDF5 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] From a drug delivery perspective, polymeric depot compositions generally suffer from the disadvantages of accepting only relatively low drug loads and having "burst / lag" release profiles
This is a highly potent formulation, but the concentration of active agent that can be included in the formulation is limited by its solubility

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Somatostatin receptor agonist formulations
  • Somatostatin receptor agonist formulations
  • Somatostatin receptor agonist formulations

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0289] Example 1: Solubility Screening

[0290] Placebo lipid mixture formulations as well as individual individual lipid formulations were prepared in 10R vials according to Table 1 . The sample size is 6g. Samples of each formulation type of SOM230 (pasiretide pamoate) with 3 wt% (corrected peptide purity and content) drug loading were prepared in 2R vials except Form 15 where only 1 wt% S230 was evaluated preparation. Samples were allowed to equilibrate at ambient room temperature; samples with Formulations 1-8 were rotated end-over-end, samples with Formulations 9-12 were magnetically stirred. The flowchart in Figure 1 describes the sample preparation process. Screening covered the following formulation variables:

[0291] ●Lipid weight ratio (SPC / GDO weight ratio)

[0292] ●Co-solvent nature and concentration

[0293] ●Single lipid formulation

[0294] ●Single solvent (PG only)

[0295] Table 1. Composition (% by weight) of placebo lipid formulations used for solu...

Embodiment 2

[0309] Example 2 - Syringability, Density and Viscosity

[0310] Formulations according to Table 3 were prepared and used to evaluate injectability, density and viscosity. Lipid / SOM230 formulations with drug loadings of 3 and 6 wt%, respectively, were prepared in 15R injection glass vials.

[0311] Table 3. Composition (% by weight) of lipid / SOM230 formulations.

[0312]

[0313] *Pamoate; when corrected for peptide purity and content, 4.3, 5.9, 7.4 and 8.6 wt% SOM230 pamoate corresponded to approximately 30, 40, 50 and 60 mg SOM230 free base / g, respectively.

[0314] The sample preparation procedure is described in Figure 1. A magnetic stir bar was added to the sample (sample size 6 g) followed by magnetic stirring at ambient room temperature. Samples were investigated by visual inspection and the approximate time to complete dissolution was recorded.

[0315] The formulation with 30 mg / g was clear and homogeneous within 48 hours. The sample with 60 mg / g was homogeneo...

Embodiment 3

[0334] Embodiment 3-contrast preparation research with acetic acid SOM230 and hydrochloride SOM230

[0335] Preparation of hydrochloric acid SOM230

[0336] SOM230 hydrochloride was prepared from SOM230 acetate using the ion exchange method. An ion exchange column was prepared by placing glass wool (HPLC grade) in the bottom of a 200 mL glass chromatography column from Sigma-Aldrich. Approximately 20 mL of a mixture of Dowex 1x2 chloride form (Sigma-Aldrich) and distilled water (1:1 by volume) was added, followed by a piece of glass wool placed on top of the column. Rinse the column with distilled water and measure the conductivity. When the conductivity is below 35 μS / em, add a volume of 40 mL WFI to the column.

[0337] For ion exchange, a sample of SOM230 acetate (SOM230(Ac)) was prepared in a 100 mL Pyrex flask. Samples were diluted with WFI to a final volume of 65.55 mL and a concentration of 3.8 mg SOM230(Ac) / mL. Transfer the SOM230(Ac) solution to the ion exchange ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to compositions forming a low viscosity mixture of: a) 20-50 wt.% of at least one diacyl glycerol; b) 20-54 wt.% of at least one phosphatidyl choline (PC); c) 5-15wt.% of at least one biocompatible, organic mono-alcoholic solvent; d) 1 to 20 wt.% polar solvent e) 5 to 150 mg / ml of at least one peptide somatostatin receptor agonist comprising pasireotide; f) optionally at least one antioxidant; wherein the ratio of components a:b is in the range 40:60 to 54:46; wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with excess aqueous fluid. The invention further relates to methods of treatment comprising administration of such compositions, and to pre-filled administration devices and kits containing the formulations.

Description

field of invention [0001] The present invention relates to formulation precursors (preformulations) for in situ production of compositions for controlled release of peptide active agents, and methods of treatment using such formulations. In particular, the present invention relates to highly loaded preformulations for parenteral application of an amphiphilic component and at least one peptide active agent, including pasiiretide, which undergo a phase transition upon exposure to aqueous fluids such as bodily fluids , thereby forming a controlled release composition. Background of the invention [0002] Many bioactive agents, including pharmaceuticals, nutraceuticals, vitamins, etc., have a "window of function". That is, there are concentration ranges over which these agents may be found to provide some biological effect. When the concentration in the appropriate part of the body (eg, locally or as indicated by serum concentrations) falls below a certain level, the agent may...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/127A61K38/00A61K47/10A61K47/14A61K47/24
CPCA61K9/0019A61K9/0024A61K9/1274A61K31/4045A61K38/12A61K38/31A61K47/10A61K47/14A61K47/183A61K47/24A61P1/04A61P1/12A61P1/18A61P3/10A61P3/12A61P5/00A61P5/02A61P13/12A61P17/06A61P19/02A61P29/00A61P35/00C07K7/64A61K38/08
Inventor 卡塔林·尼斯托尔马库斯·约翰松弗雷德里克·蒂贝里
Owner CAMURUS AB
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com